(105e) Avoiding Microreactor Clogging By Inorganic Solid Formation in Continuous Chemical Synthesis of Pharmaceutical Compounds

Authors: 
Giri, G., Massachusetts Institute of Technology
Jensen, K. F., Massachusetts Institute of Technology

Continuous manufacturing of fine chemicals and pharmaceuticals using microfluidic platforms are currently researched due to their advantageous heat and mass transfer rates compared to traditional batch processes, leading to shorter reaction times and higher yields. Palladium catalyzed C-N coupling reaction in microreactors is desirable for pharmaceutical applications but the reaction generates stoichiometric amounts of inorganic salts, which then precipitate and clog the microreactor. Biphasic reactions that can dissolve the solids can introduce mass transfer limitations or poison the catalyst. In this work, we perform a model Palladium catalyzed C-N coupling reaction in a monophasic system to show enhanced control of solid formation. We avoid microreactor clogging by tailoring the morphology of inorganic crystals, achieved through a combination of nucleation control and other mechanical means. We demonstrate the formation of crystal aggregates that can flow through the reactor without causing clogging or undesirable pressure fluctuations, and study the impact of crystal aggregate size on clogging behavior. We optimize the reaction conditions to ensure adequate conversion levels. Design strategies for ensuring reaction optimization while avoiding microreactor clogging will be presented.